The overall aims of this research are to study the mechanisms of murine arthritis induced by M. arthritidis and to apply this knowledge to further understand the etiology and immunological dysfunction of human rehumatoid arthritis. More specifically investigations will include: 1. The mechanisms of mouse disease induced by M. arthritidis in respect to the role of mitogens in toxic death and acute and chronic arthritis induced by this organism. Studies to determine the immunological abnormalities induced by the administration of mitogens. 2. The genetic control of mouse and rat arthritis and its relationship to background or genes of the major histocompatibility comples. Multiple inbred, congenic and recombinant animal strains will be used. 3. To determine the relationship between Ir gene control of muring lymphocyte activation and the role of HLA.DR antigens in predisposing to human reheumatoid arthritis. 4. To isolate an agent from human rheumatoid tissues utilizing latest methodology. These studies have considerable implications for human disease since the arthritogenic mycoplasmas exhibit inflammatory pathways similar to those demonstrated in human RA. Moreover the new studies provide a link to further understanding the nature of HLA.DR associations with rheumatic disease.